However, as the activity of Cdk1 in G2 is low, it is possible to speculate that in addition to Cdk1, other kinases might phosphorylate GRASP65 to generate a Plk1 binding side.
This additional fragmentation step depends on the unstacking of the Golgi membranes, followed by an additional vesiculation step. In cell-free systems, mitotic disassembly of Golgi cisternae occurs concomitant to unstacking, and can follow two distinct pathways. Concomitantly, a COPI-independent pathway breaks up the flattened cisternae into tubular-vesicular fragments Shorter and Warren, The nature of these fragments and the mechanisms of their inheritance in the two daughter cells have been described according to two opposing models.
The first model suggests that the Golgi complex is in dynamic equilibrium with the ER, and thus a block of membrane transport in mitosis would induce Golgi membrane disassembly Zaal et al.
In prophase, Cdc2-mediated inactivation of Sar1 would reduce the export of membranes and proteins from the ER Prescott et al. As a consequence, the membrane transport cycle between the Golgi complex and the ER would be impaired, which would induce progressive redistribution of Golgi membranes into the ER. The rate of this accumulation would be further enhanced by increased protein transport from the Golgi to the ER in the initial phases of mitosis, after dissociation of Arf1 from the Golgi membranes Altan-Bonnet et al.
This model finally suggests that the Golgi is inherited together with the ER Zaal et al. The second model suggests that the mechanism of Golgi inheritance is achieved in an ER-independent manner. Thus, it indicates that the Golgi complex is an autonomous organelle that forms the mitotic Golgi remnants required for post-mitotic reassembly Barr, In this case, the key event of Golgi inheritance is the disruption of the membrane tethering complexes by mitotic-activated kinases Shorter and Warren, As a result, the Golgi stacks are fragmented into tubular-vesicular clusters and the small vesicles of the Golgi haze, which are then actively partitioned between the two daughter cells in a mitotic-spindle-mediated process Shima et al.
According to this model, at the end of mitosis, inhibition of mitotic kinases would reverse this series of events to allow the Golgi to be reassembled. Many pieces of evidence support the second ER-independent Golgi partitioning model. Indeed, it has been shown that mitotic Golgi fragments accumulate near the spindle poles, while the ER is not present in the spindle area Puri et al. Additionally, Seemann and co-workers provided evidence in favor of spindle-dependent Golgi ribbon inheritance Wei and Seemann, Indeed, through induction of asymmetric cell division where the spindle was inherited by only one of the daughter cells, they demonstrated that the Golgi reassembled into a ribbon only in the cell with the inherited spindle.
Conversely, in the spindle-deprived cell, the Golgi stacks remained dispersed throughout the cytoplasm Wei and Seemann, Interestingly, the injection of Golgi protein extracts into these spindle-deprived cells with the addition of purified spindle proteins promoted the reforming of an intact Golgi ribbon Wei and Seemann, Thus, the accuracy of Golgi inheritance suggests the involvement of an active and regulated partitioning mechanism, instead of a stochastic process Shima et al.
In-vitro cisternal regrowth assays from mitotic Golgi fragments have identified NSF N-ethylmaleimide-sensitive factor and p97 as two key factors in post-mitotic Golgi reassembly Acharya et al.
In the post-mitotic Golgi-reassembly process, two sequential events have been suggested: first, membrane fusion induced by NSF produces large vesicles and tubular-reticular elements, which then fuse to generate cisternae through a pmediated process. During mitosis, Cdk1 phosphorylates p47, p37 and VCIP, and blocks pcontrolled membrane-fusion processes so that the Golgi membranes remain disassembled Uchiyama et al. Thus, mitotic phosphorylation of the membrane fusion machinery can explain the mitotic Golgi phenotype of dispersed tubular-reticular membranes and vesicles in the cytosol.
Additionally, ubiquitination has been shown to have an important role in post-mitotic Golgi reassembly. P47, the adaptor protein of p97, contains a UBA ubiquitin binding domain. P97 binding promotes p47 binding to ubiquitinated proteins via its UBA domain, and this domain is necessary for Golgi reassembly Meyer et al.
Indeed, it has been shown to have a deubiquitinase activity, which was necessary for Golgi reassembly Zhang and Wang, Conversely, at the end of mitosis, VCIP is dephosphorylated on Ser , and this is associated with recovery of its deubiquitinase activity and with post-mitotic Golgi reassembly Zhang and Wang, In addition to the stimulation of the fusion processes, dephosphorylation of the GRASP proteins favors the stacking and linking of the reformed Golgi cisternae, thus leading to the reassembly of the Golgi complex after mitosis.
In conclusion, the Golgi ribbon can be viewed as a metastable structure that is maintained by several core and accessory proteins, and that can rapidly adapt to stressful or physiological conditions. Part of the signaling through which a block in Golgi fragmentation prevents cell-cycle progression has been identified.
Interestingly, a block in Golgi fragmentation interferes with Aurora-A recruitment to the centrosome in G2, and prevents its activation Persico et al. This link between Golgi organization in G2 and Aurora-A recruitment and activation provides the first mechanistic insight into how Golgi dynamics can be coordinated with cell-cycle progression.
However, a second cyclinB-dependent, but Aurora-independent, mechanism might also contribute to Golgi-mediated control of mitotic entry. Both CycB1 and CycB2 cooperate to promote mitotic entry. It is possible that activation of the Golgi-associated CycB2-Cdk1 complex is regulated by inhibition of Golgi-localized Myt1 Villeneuve et al.
More investigations are required to address this issue. There is evidence that complete disassembly of the stacks is not required for mitotic progression Uchiyama et al. Also, the second step of Golgi fragmentation in mammals i. Indeed, during prophase, disassembly of the Golgi stacks correlates with release of Arf1 and a set of peripheral proteins from the Golgi membranes Altan-Bonnet et al.
Arf GTPases are key regulators of membrane traffic and organelle structure, and they act through regulation of the recruitment of a large number of effectors. These include components of vesicular coats, membrane tethers, and lipid-binding or lipid-modifying enzymes Cherfils, The mechanism through which Arf1 is released from Golgi membranes has started to emerge more recently.
This results in the release of Arf from the Golgi membranes, but surprisingly, this does not cause the release of COPI, one of the main Arf effectors for membrane traffic Morohashi et al. Golgin is among the key Golgi-located Arf effectors, and it recruits the dynein motor to regulate the position of the Golgi complex Yadav et al.
The minus-end-directed motor is required to confer centripetal motility to membranes. During cell division, the association of the dynein motor with membranes is regulated by dissociation of the receptor—motor complex from the membranes, which can explain the dramatic changes in organelle positioning observed during mitosis Yadav et al. Proteins of the Rab family have also shown to have links to Golgi-based processes and mitotic progression.
Rab6A' regulates retrograde transport from late endosomes via the Golgi to the ER, and it is involved in the transition from metaphase to anaphase during mitosis.
Bicaudal-D1 is an important effector of Rab6B Wanschers et al. Rab6B and Bicaudal-D1 co-localize at the Golgi complex and on vesicles, where they regulate the association of these membranes with microtubules. Rab11 is localized at the trans -Golgi network and late endosomes during interphase.
During mitosis, Rab11 localizes to the mitotic spindle and regulates dynein-dependent endosome localization at the mitotic spindle poles Hehnly and Doxsey, Rab11 depletion prevents localization of recycling endosomes at the spindle poles, delays mitotic progression, disrupts spindle-pole protein recruitment and astral microtubule organization, and alters mitotic spindle orientation. This suggests that Rab11 is a crucial regulator of correct spindle-pole function during mitosis.
Altogether, these findings indicate that during mitosis, and concomitant with the disassembly of Golgi stacks, a series of GTP-binding proteins regulate the changes in the localization and function of Golgi-localized proteins, to regulate the key mitotic events. This suggests that Golgi disassembly is coordinated with chromosome segregation. Related to this hypothesis, the Golgi-associated protein p has been shown to dissociate from the Golgi complex during mitosis.
Instead, p partitions with the poles of the mitotic spindle, where it controls spindle formation and chromosome segregation and cytokinesis Radulescu et al. At the spindle, microtubule nucleation is also favored by GM, thus functionally linking Golgi membranes to spindle formation, which is crucial for faithful chromosome inheritance Wei et al. As a further example of a functional link between Golgi fragmentation and spindle formation, Miki is a Golgi-associated protein that is relocated during mitosis to the centrosome.
Thus, Golgi vesiculation can be explained by the need to change the subcellular distribution of proteins that acquire specific and novel functions during mitosis. The Golgi membranes begin to reassemble during telophase, at which time they form two distinct ribbons on the opposite sides of the nucleus in each daughter cell Altan-Bonnet et al. The larger Golgi ribbon is positioned next to the centrosome, while the smaller one is in close proximity to the midbody.
During cytokinesis, the smaller Golgi ribbon migrates to the opposite side of the nucleus and fuses with the larger Golgi ribbon. Overall these data suggest that a functional Golgi ribbon might be required to establish asymmetric cell division. In conclusion, mitotic partitioning of the Golgi complex is composed of individual and consecutive steps that control different aspects of cell division Figure 1. G2-specific fragmentation of the Golgi ribbon into isolated stacks is necessary for cell entry into mitosis.
Then, during mitosis, selected Arf and Rab GTPases regulate the disassembly of the isolated stacks and the relocation of Golgi-associated proteins. This regulates the events that are necessary for successful cell duplication, such as spindle formation and chromosome segregation.
These will have the potential to reveal novel targets and approaches for pharmacological intervention in many diseases, including cancers. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The authors apologize to all colleagues whose work it has not been possible to cite in this review, due to space limitations.
The authors also thank Chris Berrie for editorial assistance. Acharya, U. The formation of Golgi stacks from vesiculated Golgi membranes requires two distinct fusion events. Cell 82, — Signaling via mitogen-activated protein kinase kinase MEK1 is required for Golgi fragmentation during mitosis. Cell 92, — Altan-Bonnet, N. A role for Arf1 in mitotic Golgi disassembly, chromosome segregation, and cytokinesis. Molecular basis for Golgi maintenance and biogenesis.
Cell Biol. Golgi inheritance in mammalian cells is mediated through endoplasmic reticulum export activities. Cell 17, — Axelsson, M. Rapid, endoplasmic reticulum-independent diffusion of the mitotic Golgi haze. Cell 15, — Barr, F. Golgi inheritance: shaken but not stirred. Beams, H. The Golgi apparatus: structure and function. Brunger, A. FEBS Lett. Cervigni, R. Cell Sci. Cherfils, J. Arf GTPases and their effectors: assembling multivalent membrane-binding platforms.
Colanzi, A. Mitosis controls the Golgi and the Golgi controls mitosis. Closer scrutiny of micrometer- and nanometer-sized subcellular structures was later enabled by the rise of electron microscopy, which illuminated the complexity of organelles and their varying positions within the cell. The current use of fluorescent antibodies coupled with three-dimensional imaging using confocal microscopy allows us to observe these organelles via time-lapse images and reveals how they function in living cells.
Other key techniques are the use of differential centrifugation to purify components, autoradiography to follow processes over space and time, biochemistry to understand what each component is doing at the molecular level, and the use of inhibitors to selectively turn key events on and off and observe the outcome.
Finally, genetics, in all its forms, has allowed us to dissect the structure and function of these subcellular compartments by selective disruption of individual cell components. The more all these structures are studied, the more it becomes clear how they all interact in a variety of ways e. Future research in these areas of cell biology are likely to continue current trends.
For instance, the role of primary cilia and intraflagellar transport are two rapidly growing areas, with implications for treatment of various disorders, including cancer. Research into alternative energy sources will certainly pay attention not only to the role of mitochondria and chloroplasts, but also to less known organelles such as the hydrogenosome, which makes hydrogen.
Cell Membranes. Microtubules and Filaments. Endoplasmic Reticulum, Golgi Apparatus, and Lysosomes. Plant Cells, Chloroplasts, and Cell Walls. How Viruses Hijack Endocytic Machinery. Discovering the Lipid Bilayer. Discovery of the Giant Mimivirus.
Endosomes in Plants. Mitochondria and the Immune Response. Plant Vacuoles and the Regulation of Stomatal Opening. The Discovery of Lysosomes and Autophagy. These newly modified proteins and lipids are then tagged with phosphate groups or other small molecules so that they can be routed to their proper destinations.
Finally, the modified and tagged proteins are packaged into secretory vesicles that bud from the trans face of the Golgi. While some of these vesicles deposit their contents into other parts of the cell where they will be used, other secretory vesicles fuse with the plasma membrane and release their contents outside the cell.
In another example of form following function, cells that engage in a great deal of secretory activity such as cells of the salivary glands that secrete digestive enzymes or cells of the immune system that secrete antibodies have an abundance of Golgi.
In plant cells, the Golgi apparatus has the additional role of synthesizing polysaccharides, some of which are incorporated into the cell wall and some of which are used in other parts of the cell. Many diseases arise from genetic mutations that prevent the synthesis of critical proteins. One such disease is Lowe disease also called oculocerebrorenal syndrome, because it affects the eyes, brain, and kidneys.
In Lowe disease, there is a deficiency in an enzyme localized to the Golgi apparatus. Children with Lowe disease are born with cataracts, typically develop kidney disease after the first year of life, and may have impaired mental abilities. Lowe disease is a genetic disease caused by a mutation on the X chromosome.
Females possess two X chromosomes while males possess one X and one Y chromosome. In females, the genes on only one of the two X chromosomes are expressed. However, males only have one X chromosome and the genes on this chromosome are always expressed.
Therefore, males will always have Lowe disease if their X chromosome carries the Lowe disease gene. The location of the mutated gene, as well as the locations of many other mutations that cause genetic diseases, has now been identified. Through prenatal testing, a woman can find out if the fetus she is carrying may be afflicted with one of several genetic diseases.
Geneticists analyze the results of prenatal genetic tests and may counsel pregnant women on available options. They may also conduct genetic research that leads to new drugs or foods, or perform DNA analyses that are used in forensic investigations.
Improve this page Learn More. Skip to main content. Module 4: Cellular Structure. Search for:. Endomembrane System Learning Outcomes Describe the structure, function, and components of the endomembrane system.
0コメント